PubMed Health⌕ Search

Biomedical subjects

J Birkmann

Publications and source records attributed to J Birkmann.

At least 19 recordsLinked to original sources
PubMed2006

Prospective trial on topotecan salvage therapy in primary CNS lymphoma.

BACKGROUND: Standard salvage therapy has not been established for recurrent primary central nervous system lymphoma (PCNSL). We report the final results of a prospective study on topotecan chemotherapy in relapsed or refractory PCNSL. PATIENTS AND METHODS: The study included 27 patients with a median age of 51 years and an ECOG performance status of 2. Fourteen patients were refractory to the last therapy, and 13 relapsed after a median period of 6.0 months. Pretreatment with up to four regimens included chemotherapy in 26 patients and whole brain irradiation in 14. A 30-min daily topotecan infusion of 1.5 mg/m(2) for 5 days was repeated every 3 weeks. RESULTS: The response rate was 33% with five complete (CR) and four partial remissions (PR). The median follow-up was 37.7 months. All complete responders had sustained remissions lasting for 9 to 28 months. The median event-free survival (EFS) was 2.0 months (9.1 months in responders), the overall survival (OAS) was 8.4 months. CTC grade 3-4 leukopenia occurred in 26% and thrombocytopenia in 11% of the patients. Eight of 12 patients alive without cerebral lymphoma > or = six months after topotecan exhibited deficits attributable to late neurotoxicity. CONCLUSION: Topotecan as monotherapy is active in relapsed and refractory PCNSL with tolerable toxicity.

Adult↗
PubMed2006

A therapeutic platelet transfusion strategy is safe and feasible in patients after autologous peripheral blood stem cell transplantation.

Prophylactic platelet transfusions are considered as standard in most hematology centers, but there is a long-standing controversy as to whether standard prophylactic platelet transfusions are necessary or whether this strategy could be replaced by a therapeutic transfusion strategy. In 106 consecutive cases of patients receiving 140 autologous peripheral blood stem cell transplantations, we used a therapeutic platelet transfusion protocol when patients were in a clinically stable condition. Platelet transfusions were only used when relevant bleeding occurred (more than petechial). Median duration of thrombocytopenia <20 x 10(9)/l and <10 x 10(9)/l was 6 and 3 days, which resulted in a total of 989 and 508 days, respectively. In only 26 out of 140 transplants (19%), we observed clinically relevant bleeding of minor or moderate severity. No severe or life-threatening bleeding was registered. The median and mean number of single donor platelet transfusions was one per transplant (range 0-18). One-third of all transplants, and 47% after high-dose melphalan could be performed without any platelet transfusion. Compared with a historical control group, we could reduce the number of platelet transfusions by one half. This therapeutic platelet transfusion strategy can be performed safely resulting in a considerable reduction in prophylactic platelet transfusions.

Adolescent↗
PubMed2002

Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma.

We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT. A total of 50 patients (94%) were consolidated in complete ( n=25) or partial ( n=25) remission, whereas 3 patients had chemoresistant disease before Bu/Cy/VP-16. Thirty-five patients (66%) had received prior radiotherapy (RT) excluding total body irradiation (TBI) as part of the conditioning regimen. The main nonhematological toxicities (grade II-IV according to the Bearman score) in 52 evaluable patients were mucositis (79%) and hepatic toxicity (15%). Severe veno-occlusive disease (VOD) occurred in three patients (5.8%) including one treatment-related death caused by VOD. Overall, treatment-related mortality was 3.8%. After a median follow-up for surviving patients of 21 months (range: 6-118), 20 patients (38%) are in continuous complete remission, 8 patients (15%) are alive in relapse, and 25 patients (47%) died. Probabilities of relapse, event-free survival, and overall survival at 3 years were 63% [95% confidence interval (CI): 48-79%], 31% (95% CI: 17-46%), and 43% (95% CI: 27-59%), respectively. In conclusion, Bu/Cy/VP-16 is an effective and well-tolerated conditioning regimen in patients with HD and NHL. Both toxicity and outcome were not significantly different in patients treated with 30 mg/kg and 45 mg/kg etoposide, respectively. The observed long-term results are even comparable to those published for other established high-dose protocols, including TBI-based regimens. However, further investigations are necessary to evaluate the value of Bu/Cy/VP-16 as a high-dose protocol for malignant lymphoma, especially in patients who have already received extensive RT.

Adolescent↗
PubMed2001

Salvage chemotherapy with mitoxantrone, fludarabine, cytarabine, and cisplatin (MIFAP) in relapsing and refractory lymphoma.

PURPOSE: The aim of the study was to evaluate the feasibility and efficacy of the combination of mitoxantrone, fludarabine, cytarabine, and cisplatin (MIFAP) in patients with prognostically unfavorable recurrent and refractory Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). METHODS: Forty-six patients (median age 43 years, range 18-63) with relapsed (n = 15) or refractory (n = 31) malignant lymphoma were enrolled (HD, n = 13; low-grade/transformed NHL, n = 4; high-grade NHL, n = 29). A total of 39 patients (85%) showed multiply relapsed diseases with a duration of prior remission of < 12 months (n = 8) or had lymphoma being resistant to prior chemotherapy (n = 31). The MIFAP therapy consisted of fludarabine (15 mg/m2, q. 12 h, day 1-4), cytarabine (50 mg/m2 by continuous infusion (CI) over 22 h, day 1-4), cisplatin (25 or 30 mg/m2 by CI over 24 h, day 1-4), and mitoxantrone (4 mg/m2, day 2-5). RESULTS: Thirteen patients (28%) achieved complete remission (CR) and 15 patients (33%) partial remission (PR), for an overall response (OR) rate of 61%. Twenty-two patients responding to MIFAP (10 CR, 12 PR) have been consolidated by high-dose therapy (HDT) with hematopoietic stem cell transplantation (SCT). After a median follow-up of 12 months, 16 patients are in continuous CR (CCR) (n = 14) or CCRu (unconfirmed) (n = 2). The median duration of event-free survival (EFS) and overall survival (OS) were 6.5 and 19.3 months, respectively. Probabilities of EFS and OS after 3 years were 19% and 40%. Responders consolidated by subsequent HDT showed rates for 3-year EFS and OS of 40% and 66%, respectively. Unfavorable prognostic factors for EFS by univariate analysis were refractory lymphoma and the presence of B-symptoms. Significant prognostic factors for OS were NHL, refractory lymphoma, B-symptoms, and bone marrow involvement. The major toxicities were leukocytopenia and thrombocytopenia of the World Health Organization (WHO) grade IV in nearly all courses (median duration 10 and 11 days). In contrast, non-hematological side effects were moderate, predominantly of WHO grades I and II. Treatment-related mortality with MIFAP was 4% (two patients with septicemia by Aspergillus fumigatus). CONCLUSIONS: MIFAP is an effective salvage protocol for patients with poor-risk recurrent or refractory HD and NHL. The observed toxicity seems to be acceptable considering the unfavorable prognosis and intensive pretreatment. The results in patients responding to MIFAP and afterwards undergoing HDT with autologous stem cell support are even comparable to those published in patients with prognostically more favorable diseases.

Adolescent↗
PubMed1999

Sequential cycles of high-dose chemotherapy with dose escalation of carboplatin with or without paclitaxel supported by G-CSF mobilized peripheral blood progenitor cells: a phase I/II study in advanced ovarian cancer.

To assess high-dose carboplatin chemotherapy with or without paclitaxel with filgrastim mobilized peripheral blood progenitor cell (PBPC) support in a phase I/II study, a total of 21 patients with mostly chemonaive disease received four cycles of high-dose chemotherapy. Cycle 1 (cyclophosphamide, 6 g/m2) was followed by two cycles of carboplatin (1600 mg/m2 or 1800 mg/m2). Cycle 4 consisted of carboplatin (1600 mg/m2), etoposide (1600 mg/m2), and melphalan (140 mg/m2). Further chemotherapy intensification was achieved by adding paclitaxel (175 mg/m2) to all cycles with a fixed carboplatin dose (1600 mg/m2). Ototoxicity was dose-limiting for escalation of sequential cycles of carboplatin. Grade 2 and grade 3 ototoxicity, hearing loss not requiring a hearing aid, or hearing loss correctable with a hearing aid, was observed with carboplatin at 1800 mg/m2. The maximum tolerated dose (MTD) of sequential carboplatin, therefore, was identified in this study as 1600 mg/m2. After cycles 1, 2, 3 and 4 the median duration of leukopenia (<1.0x10(9)/l) was 7, 4, 4 and 6 days. Severe grade 3 and 4 infections were seen in only 7% of cycles. Of the 21 patients evaluable for disease response, 57% had complete remissions and 43% experienced partial remissions resulting in an overall response rate of 100%. The median progression-free survival is 25 (15-36) months, the median overall survival 36.5 (15-38) months. Most patients were suboptimally debulked or had bulky residual disease at the start of chemotherapy. Sequential high-dose chemotherapy to a maximum dose of 1600 mg/m2 carboplatin is effective and feasible. A randomized, prospective trial comparing sequential high-dose chemotherapy with optimal standard chemotherapy is now warranted.

Adult↗
PubMed1999

The use of CD34+-selected PBPC after high-dose chemotherapy in breast cancer patients is associated with prolonged recovery time and increased infectious complications.

High-dose chemotherapy with autologous stem cell rescue can result in autotransplantation of tumor cells. A possible approach to reduce tumor cell contamination is the positive selection of CD34+ PBPC, but this might be associated with a prolonged recovery time as well as an increased risk of infectious complications because of the loss of committed progenitor cells. To investigate this aspect, we compared two sequentially treated cohorts of high-risk breast cancer patients. Both groups received the same high-dose chemotherapy regimen followed by autologous peripheral stem cell transplantation. Group I received CD34+-selected blood progenitor cells, and group II received nonselected blood progenitor cells. We compared these two identically treated groups with regard to recovery time, need for blood products, infectious complications, need for antibiotic treatment, and length of the transplantation-related hospital stay. We found a prolonged recovery time for neutrophils up to 0.5 x 10(9)/L (14 days in the selected group/10 days in the nonselected group) and platelets up to 30 x 10(9)/L (29/12 days), associated with an increased requirement for RBC transfusions (5/3 U) and platelet transfusions (10/2 U). The rate of severe infectious complications (2/0), the need for nonprophylactic antibiotic treatment (15/10), and the length of the hospital stay (25/21 days) in group I were also increased. We conclude that positive selection of PBPC should not be used routinely until randomized studies show a clear long-term benefit of using CD34+-selected stem cell products in breast cancer patients.

Antigens, CD34↗
PubMed1998

Bestfallanalysen zu 4 aktuellen unkonventionellen Behandlungsverfahren in der Onkologie.

Best-Case Analyses of 4 Current Unconventional Therapies in OncologyBest-case analyses are - under certain circumstances - a useful method to decide on the tumor-specific efficacy of unconventional treatments, without performing formal clinical studies and with limited expenditure. As part of the activities of the 'Arbeitsgruppe Biologische Krebstherapie', sponsored by the 'Deutsche Krebshilfe', an analysis and second-opinion judgement (according to internationally accepted standards) of their 'best cases' was offered to 36 manufacturers and users of unconventional cancer drugs and methods, who in public propagated these as effective cancer therapies. Only few of the approached offerers were both willing to cooperate and able to provide significant documentation for such an analysis. Therefore, only four best-case analyses could be performed completely. The work-up of the available documentation was not very convincing in all four cases, especially when considering that a positive selection from hundreds or even thousands of applications had taken place. The results of the analyses did not reveal any well-founded evidence for a tumor-specific effectiveness of the corresponding applications. The discrepancy between the offerers and the working group's judgements results especially from the circumstance that the majority of the treatments were not performed on patients with advanced tumor disease without any other conventional therapies, but additionally to established therapies or as an adjuvant treatment protocol. Other reasons were the obvious misjudgement of findings, the assessment of unimportant or unsuitable parameters, the misinterpretation of the probably normal development as a treatment success or also documentation inappropriate for evaluation.

Journal Article↗
PubMed1997

Effects of recombinant human thrombopoietin alone and in combination with erythropoietin and early-acting cytokines on human mobilized purified CD34+ progenitor cells cultured in serum-depleted medium.

The effects of recombinant thrombopoietin (TPO) alone and in combination with erythropoietin (EPO) and early-acting cytokines such as interleukin 3 (IL-3), stem cell factor (SCF) and GM-CSF on highly purified mobilized human CD34+ progenitor cells were studied in a serum-depleted culture system. Eight leukapheresis samples were cultured for seven days and analyzed; aliquots were replated and re-evaluated on day 12. Three-color flow cytometry was used together with morphologic analysis to determine proliferation and megakaryocytic or erythroid maturation. TPO alone was sufficient for cell survival and proliferation in serum-depleted medium. In the absence of other growth factors, almost all CD34+ cells differentiated along the megakaryocytic pathway within 12 days. Concomitantly, the progenitor cells gradually acquired the morphologic features of mature megakaryocytes. After exposure to TPO for one week, 50% of the cells still expressed CD34; by day 12 the remaining CD34+ cells (11%) were all coexpressing CD41. TPO alone did not support proliferation of glycophorin-A-positive cells. The addition of TPO to early-acting cytokines (EPO, GM-CSF, SCF and/or IL-3) not only increased the overall megakaryocyte expansion, but also generated a different maturation pattern of the CD41+ megakaryocyte progenitors. It further doubled the number of erythroid cells and c-kit+ cells in the second week of culture. Interestingly, the overall number of CD34+ cells was increased about fivefold when TPO was added to the early-acting cytokines, with a marked expansion of the CD34+/CD41+ and CD34+/CD117+ subpopulations. TPO can augment the pool of committed progenitors, thereby increasing the number of its own target cells and the number of EPO-responsive cells. These properties make TPO an interesting cytokine for the ex vivo expansion of human progenitor cells.

Antigens, CD34↗
PubMed1997

Complete spontaneous remission in a patient with metastatic non-small-cell lung cancer. Case report, review of the literature, and discussion of possible biological pathways involved.

Spontaneous remission of cancer (SR) is defined as a complete or partial, temporary or permanent disappearance of all or at least some relevant parameters of a soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression. We report the case of a 61-year-old man who presented with extensive metatastic disease five months after pneumonectomy for poorly differentiated large cell and polymorphic lung cancer. A vast metastatic tumour mass of the abdominal wall was confirmed histolologically and there was clinical and radiographic evidence of liver and lung metastases. Eight months later, the patient was operated on for a hernia, which had developed in the inguinal biopsy scar and the surgeon confirmed complete clinical SR of the abdominal wall metastases. Again five months later there was no longer any radiologic evidence of liver and lung metastases. Complete remission has persisted more than five years. Histology of the primary and of the abdominal metastases were reviewed by several independent pathologists. SR is an extremly rare event in lung cancer. This is the first documented case of clinically evident visceral metastases of a bronchiogenic adenocarcinoma developing after complete resection of the primary and then showing complete SR. The epidemiology of SR is reviewed and possible mechanisms involved in SR are discussed.

Apoptosis↗
PubMed1996

LW/SO cell line: a tool for studying the phenotypical characterization and commitment of hematopoietic stem cells.

We report our observations with the cell line LW/SO, which was recently derived from the bone marrow of a patient with acute myeloid leukemia. Based on the morphological and histochemical examination, the leukemic cells were classified primarily as FAB type M4. However, 2 years later, in relapse, the cells changed their morphology and were hence specified as FAB type M2 (slightly positive for acid phosphatase and Sudan black). The cells established have now been in culture for approximately 11 months and display nearly 100% CD4/5/7/15/25/71/120a,b at varying densities. Some of them spontaneously and reversibly become either CD34 + /38- or CD34 - /38+, yet the majority of the cells remain negative for both. All attempts to separate the cells with a distinct phenotype by limiting dilution or sorting through a flow cytometer failed repeatedly. The subsets, enriched up to 98% (regardless of their primary immunophenotype CD34 - / 38-, CD34 + /38-, or CD34 - /38+), soon displayed a phenotypical constellation similar to that before sorting. The ratio of CD34- to CD34+ seems to be influenced by the cell density: The greater the cell-to-cell contact, the lower the percentage of CD34-expressing cells. Some of the cells apparently differentiate into T-cell phenotype and acquire CD3 and T-cell receptor (TCR) alpha/beta molecules. While the quantity of CD34-expressing cells significantly increased in the presence of dexamethasone (10(-7) M), and some of them additionally acquired CD33 antigen, the percentage of CD3-positive cells was enhanced by adding 1% DMSO in medium. In contrast, cytokines such as IL-1, IL-2, IL-3, IL-4, IL-6, G-CSF, GM-CSF, or SCF (c-kit ligand) altered neither the proliferation capacity nor the phenotypical constellation of LW/SO cells (each tested alone). Although normal karyotype was obtained from the bone marrow cells, the LW/SO cells revealed a homogeneous chromosomal composition of 45, X, -X, der(9) inv(9) (p12q13) del(9) (p22?). These data suggested that LW/SO cells might be the leukemic counterpart of putative pre-CD34-positive progenitors. In order to substantiate this assumption, we analyzed the expression of other so-called T-cell markers on CD34+ cells from peripheral blood stem cell aphereses of five patients who later underwent high-dose chemotherapy and subsequent stem cell retransfusion. These data clearly revealed that a considerable amount of CD34+ hematopoietic progenitors co-express CD2/4/(5)/(7)/25 at an early stage of differentiation, and support the notion that CD34-negative LW/SO cells with the surface markers CD4/5/7/25 are probably phenotypical representatives of pluripotent stem cell. Hence, not all CD34-negative populations with so-called T-cell surface markers should be considered T-cells; some may constitute the ancestor of CD34 antigen-expressing progenitors.

ADP-ribosyl Cyclase↗
PubMed1994

Randomised comparison of CHOEP versus alternating hCHOP/IVEP for high-grade non-Hodgkin's lymphomas: treatment results and prognostic factor analysis in a multi-centre trial.

BACKGROUND: With CHOP, the standard protocol of recent decades, about 30% of long-term survival has been reported. A number of studies using more aggressive multidrug regimens or alternating chemotherapies have recently suggested higher CR rates and increased survival. In 1989 we reported similar results with a combined-modality treatment administering 6 cycles of CHOP supplemented with etoposide and an involved field irradiation for patients in PR or CR. PATIENTS AND METHODS: To confirm the efficacy of this approach, we initiated a prospective randomised trial comparing 4 cycles of CHOP-VP16 (CHOEP) with 4 cycles of two alternating regimens, 'hCHOP and IVEP'. One hundred seventy-five patients with high-grade non-Hodgkin's lymphomas stages II-IV were stratified for age, stage and LDH and randomised to receive either four cycles of cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone (CHOEP) in arm A or four cycles of chemotherapy with a dose-intensified CHOP (hCHOP) alternating with ifosfamide, etoposide, vindesine, prednisolone (IVEP) in arm B. After four cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission. RESULTS: Of the 185 randomised patients, 175 were eligible and 171 evaluable for response and survival. One hundred forty-six of the 171 patients (85%) achieved complete remission (CR) with 87% and 84% CRs in arms A and B, respectively. With a median follow-up of 36 months the estimated overall survival at 2 years is 66% and 73% for arms A and B, respectively. The percentage of all patients in first CR is estimated to be 59% and 55% at 2 years for arms A and B, respectively. None of the differences in CR rate, survival, or relapse-free survival are statistically significant. Multivariate analysis of subgroups incorporating the factors of sex, age, performance status, stage, B symptoms, bulky disease, LDH and histology revealed that only stage and LDH were factors which independently affected outcome. The estimated 2-year survival rate of patients with stages II, III and IV is predicted to be 84%, 62% and 52%, respectively. Patients with LDH > 250 U/l have an estimated survival of 52% at 2 years versus 84% for patients with LDH < or = 250 U/l. According to the newly proposed international score system, the 2-year survival was 81% for low-risk-, 64% for low intermediate risk-, 50% for high intermediate risk-, and 43% for high-risk patients. The toxicity in both arms was tolerable. Three patients died of treatment-related causes (2 in arm A, 1 in arm B). The main toxicity was haematological with 75% of patients suffering from grades 3 or 4 neutropenia at some point during treatment. CONCLUSIONS: We observed no superior benefit for alternating regimens, and conclude that both are effective treatment protocols for aggressive histologic-type malignant lymphomas. The results obtained with four cycles of poly-chemotherapy followed by an involved field irradiation are comparable to programs using more aggressive and/or prolonged chemotherapy.

Adolescent↗
PubMed1993

Clonal growth of functionally normal and deficient neutrophils from the bone marrow of a patient with variant chronic granulomatous disease. Lack of reconstitution of oxidative burst defect by G-CSF, GM-CSF, and IFN-gamma in vitro.

To evaluate the effect of colony-stimulating factors and interferon gamma on the oxidative burst capacity of neutrophils in chronic granulomatous disease (CGD) we studied the neutrophils of a patient with variant CGD both from peripheral blood and from bone marrow culture on day 7 and 14. The results revealed that preincubation of peripheral neutrophils for 24 h in medium containing recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and recombinant human interferon gamma (rhIFN-gamma) alone or in combination did not improve the maximal oxidative burst activity measured by MTT assay. The colonies of this patient formed in agar assay were either composed of predominantly nitroblue tetrazolium (NBT)-positive cells or completely unable to reduce NBT. Despite variable colony numbers in the presence of different cytokines, the rate of NBT-positive colonies was less than 17% of the total number of colonies. However, more than 72% of the colonies were NBT positive in controls. In liquid culture, bone marrow cells yielded a comparable rate of NBT-positive and -negative populations at day 7. These data indicate that rhG-CSF, rhGM-CSF, and rhIFN-gamma alone or rhG-CSF and rhGM-CSF in combination with rhIFN-gamma are not able to reconstitute the oxidative burst defect in CGD in vitro. Indeed, regarding colony-forming capacity, the bone marrow cells from the patient responded to CSFs as well as those from control donors did. This fact may warrant the administration of hematopoietic growth factors, at least in variant CGD, in order to enhance the absolute number of functionally normal neutrophils.

Adult↗
PubMed1993

Increased levels of serum intercellular adhesion molecule 1 in HIV infection are related to immune activation.

Cytopathic mechanisms in human immunodeficiency virus type 1 (HIV-1) infection involve syncytia formation, and it appears likely that increased expression of intracellular adhesion molecule 1 (ICAM-1) is involved in these cell adhesion phenomena. In this study, we determined serum concentrations of soluble ICAM-1 (sICAM-1) in 27 patients with HIV-1 infection and a control group. In addition, we compared sICAM-1 values to CD4+ T-cell counts, serum beta 2-microglobulin (beta 2M) and serum neopterin levels. HIV-1-infected patients had significantly higher sICAM-1, beta 2M and neopterin levels than controls. The subgroup of patients with Walter-Reed stages 3-6 had only slightly higher sICAM-1 concentrations in serum than Walter-Reed stages 1-2. The sICAM-1 concentrations in HIV-1-seropositive patients correlated with beta 2M levels but neither with neopterin nor with CD4+ T-cell counts. Increased sICAM-1 may result from immune activation, which enhances the expression of ICAM-1 in patients with HIV-1 infection.

Adult↗
PubMed1992

Low-dose oral natural human interferon-alpha in 29 patients with HIV-1 infection: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To evaluate clinical efficacy and toxicity of low-dose oral natural human interferon-alpha (nHuIFN alpha) on CD4+ lymphocyte counts and clinical symptoms in patients with HIV-1 infection. DESIGN: Double-blind, randomized, placebo-controlled trial with crossover. SETTING: Private practice specializing in the treatment of patients with AIDS. PATIENTS, PARTICIPANTS: Only patients with HIV-1 infection and CD4+ lymphocyte counts between 200 and 500 x 10(6)/l were included for study. Thirty out of thirty-one patients at study entry completed treatment with placebo, and 29 completed nHuIFN alpha treatment. Mean patient age was 36 years (range, 25-58 years). The 30 patients included 26 men, of whom 22 were homosexual, and four women; five were drug users and none were currently on zidovudine therapy, although three had been previously. INTERVENTIONS: Patients were randomly assigned to cohorts of 10 to receive either 200 IU nHuIFN alpha once daily orally absorbed or placebo with crossover after 6 weeks. MAIN OUTCOME MEASURES: Every 2 weeks, a detailed history, physical examination, and laboratory tests, including CD4+ and CD8+ lymphocyte counts, were conducted. RESULTS: There was only a slight, transient increase in mean CD4+ lymphocyte counts after 4 weeks of treatment with nHuIFN alpha, compared with a slight decline when placebo was administered. This effect reached statistical significance in a subgroup of patients only and was not sustained after 6 weeks. There were no significant changes in weight and clinical symptoms. All patients remained HIV-1-antibody-positive. Treatment-related adverse reactions were not observed. CONCLUSIONS: Our double-blind, randomized, placebo-controlled clinical trial did not confirm a previous report of efficiency of oral nHuIFN alpha. Although non-toxic, our data do not justify the widespread use of low-dose oral nHuIFN alpha in HIV-infected patients outside controlled clinical trials.

Administration, Oral↗
PubMed1986

Leukemic samples characteristics associated with clonogenic growth.

In this study, we attempted to delineate readily assessable characteristics from 100 leukemic samples associated with in-vitro growth. Successful growth defined as production of greater than 30 clusters and/or colonies per culture dish was obtained in 68% of samples. More than 10 colonies were found in 59% and greater than 30 colonies in 51% of cultures, respectively. Leukemic cells from patients previously treated with aggressive cytotoxic chemotherapy grew significantly better than cells from untreated patients, independently of the above definitions of cloning success. Cells from peripheral blood had a weak, albeit significant growth advantage over bone marrow cells (p = 0.032) when cluster growth was taken into account for growth success. When colony growth alone was used as criterium, no growth advantage was found. The morphological subtype and the proliferation kinetics prior to cell plating did not affect cloning success. A high labeling index had predictive value for subsequent growth, but only in bone marrow cells. By multivariate analysis, we found that treatment status was the most important factor correlated with in-vitro growth.

Analysis of Variance↗
PubMed1984

Incidence of double minutes, cytogenetic equivalents of gene amplification, in human carcinoma cells.

Screening of the occurrence of double minutes (DM) was performed in more than 1,000 metaphases obtained from a total of 22 solid human breast tumours and more than 3,600 metaphases from a total of 55 malignant effusions (45 patients with different types of carcinomas). DM were observed in 15 of these breast tumor cases and in 34 of the effusions (obtained from 29 cancer patients). The percentage of cells exhibiting DM as well as the number of DM per respective cell varied widely. It could be seen that metastatic cells from malignant effusions exhibited on the average more DM per cell than did cells of primary breast carcinomas. Differences in the incidence of DM could be observed between different carcinomas as well as between different age groups. In addition, it did not appear that DM could be induced by mutagenic tumor therapy. DM are thus not a rare finding in human solid tumors but, as cytogenetic equivalents of gene amplification, they rather represent a fundamental biological characteristic of tumor development.

Breast Neoplasms↗